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The Role of Beta-Endorphin in Horses: a Review

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The Role of Beta-Endorphin in Horses: a Review Veterinarni Medicina, 56, 2011 (9): 423-429 Review Article The role of beta-endorphin in horses: a review M. Golynski1, W. Krumrych2, K. Lutnicki1 1Faculty of Veterinary Medicine, University of Life Sciences, Lublin, Poland 2National Veterinary Research Institute, Pulawy, Poland ABSTRACT: Opium alkaloids counterparts are secreted by human and animal organisms but the role of endog- enous opioid peptides in horses has not yet been fully elucidated. Endogenous opioids are involved in regulating food intake, sexual and social activity, pain relief and pain threshold regulation in horses as well as in regulating the functions of the immune system. The aim of this review is to describe the endogenous opioid system in the horse and its function during stress, illness, reproduction, and its influence on immunity and on the formation of reactive oxygen species (ROS) in horses. What is currently known concerning beta-endorphin suggests that they can be a promising diagnostic or prognostic indicator of many pathologic states in horses. Keywords: horse; endorphin; opioids Contents 1. Introduction 6. The role of beta-endorphin in immunity 2. Secretion 7. Prooxidative/antioxidative balance 3. Beta-endorphin and stress 8. Conclusions 4. Beta-endorphin in illness 9. References 5. Beta-endorphin and the reproductive system 1. Introduction endorphins and dynorphins. These bind to the fol- lowing specific opioid receptors types: MOR (m), Alkaloids originating from opium, used through- KOR (k) and DOR (d), and to the untypical orphan out centuries as common anaesthetics, are still receptor NOR causing numerous biological effects widely used nowadays. It has long been presumed in the entire organism as well as in specific organs. that these substances may have counterparts, which Endogenous opioids are involved, among others, are secreted by animal and human organisms. This in regulating food intake as well as sexual and social notion was supported by the research of Kosterlitz activity. They also exhibit pain relieving properties and Hughes, who in 1975 described the presence and regulate pain threshold in horses, similarly to of the first endogenous ligands of opioid receptors; the way they do in people (Hamra et al., 1993). The however, the role of endogenous opioid peptides in pain relieving function of opioid receptors evolved animals has not yet been fully explained (Kosterlitz as an element of the organismal defence system and Hughes, 1975). against stress. This function consisted primarily in There are presently many substances included in regulating the immune system (Stefano et al., 1998). the group of endogenous opioids, of which the most Thus, opioids may be ascribed the function of im- widely researched and best known are encephalins, munomodulators. 423 Review Article Veterinarni Medicina, 56, 2011 (9): 423–429 2. Secretion the appearance of the stressor. The authors suggest that beta-endorphin modulates the activity of the Proopiomelanocortin (POMC) is a precursor of hypothalamic-pituitary-adrenal axis, thereby regu- one of the endogenous opioid peptides – beta-en- lating ACTH secretion. Yet, the evidence brought dorphin, which is secreted in the horse by the pars forward in support of this claim is inconclusive. It intermedia of the pituitary gland. Additionally, proo- may cautiously be stated that beta-endorphin release piomelanocortin is a substance from which two oth- from the pituitary gland in horses is synchronised ers are formed: adrenocorticotropin (ACTH 18-39, with the initial phase of the stress reaction and may corticotropin-like intermediate lobe peptide – CLIP) in this way mitigate the negative results of cortisol and α-melanotropin (α-melanocyte stimulating on the organism. hormone, α-MSH) (Scott and Miller, 2003). Beta- endorphin is the strongest endogenous opioid along with the m- (MOR) and d-opioid (DOR) receptor 4. Beta-endorphin in illness ligand. The daily rhythm of beta-endorphin secretion One of the best examples of hyperbetaendorphine- is similar to that of ACTH and cortisol. The high- mia in horses is ECS (Equine Cushing’s Disease). est values of opioid were noted in morning blood Lowe (1993) reports that changes in the behaviour of samples (peak level at 9.00) (Hamra et al., 1993). affected individuals such as lethargy or submissive- Different results were obtained by Mehl et al. (1999), ness may result from increased concentrations of be- who did not note statistically significant differences ta-endorphin. According to Millington et al. (1988), in the levels of beta-endorphin examined in mares the concentration is 60 times higher in the plasma every two hours between 8 a.m. and 8 p.m. Owing to and 120 times higher in the cerebrospinal fluid of the inconsistency of research results so far, the data ECS-affected animals. Another cause of changes in published by Pell and McGreevy (1999) concerning animal behaviour connected with the opioid system the activity of beta-endorphin in horses with ster- is described by authors who compared the levels of eotypy, and the results of the study on foals by Fazio endorphins in healthy horses and horses with ster- et al. (2009) should be interpreted with caution, tak- eotypy (Pell and McGreevy, 1999). They argue that ing into consideration such factors as seasonality. At the diseased horses exhibited a congenital increased present, data on the daily rhythm of beta-endorphin sensitivity of opioid receptors. However, the claim is secretion in horses remains very limited. not fully proved as it is only based on the observation that there is a lack of statistically significant differ- ences in beta-endorphin concentrations between 3. Beta-endorphin and stress healthy and diseased horses. The concentration of beta-endorphin in blood The release of beta-endorphin into the blood in was also assayed in the case of colic diseases. Recent horses is particularly evident during the course of research conducted by a group of Finnish scholars stress reactions. A study on 42 healthy pure blood focussed on, among other questions, specifying the stallions was aimed at determining the impact of levels of circulating beta-endorphin using the RIA transport stress on the levels of beta-endorphin, method in colicky horses. Additionally, the study cortisol and ACTH (Fazio et al., 2008). An increase was concerned with assessing the usefulness of the in the levels of circulating ACTH was observed after method as an indicator of pain intensity, prognosis travelling distances of 100 and 200 kilometres and and stress (Niinisto et al., 2009). Observations were levels of cortisol were higher after traversing dis- made of 77 diseased horses divided into three groups tances of 100, 200 and 300 kilometres. However, the according to the intensity of clinical symptoms – mild, concentration of beta-endorphin was raised when moderate and acute. Groups were not uniform and compared to the basic level only after the distance included many horses with only intestinal obstruc- of 100 kilometres. After the next 100 and 200 kilo- tion and displacement. The control group consisted metres a decrease was observed which may suggest of 15 clinically healthy horses. Only ponies were ex- an effect of negative feedback signalling. It may cluded from the study; therefore, it may be assumed thus be assumed, on analysing the levels of beta- that horses of different types were used. Among the endorphin and ACTH that the release of the opioid experimental groups a significant variability of results into the blood occurs maximally one hour after was observed due to the duration of the disease and 424 Veterinarni Medicina, 56, 2011 (9): 423-429 Review Article the different ages of the animals in question. It ap- although reports concerning horses are scarce. The pears justified to trace the level of beta-endorphin in impact of beta-endorphin on the activity of the re- patients belonging to fairly uniform age groups and productive system remains largely a point of theo- relate the results to such parameters as the duration retical debate, based mainly on comparisons drawn of the disease. Moreover, many animals included in between different species. The role of the peptide in the study had been treated with pain relievers (mainly stallions, which is secreted by Leydig’s cells in the flunixine meglumine) prior to hospitalisation. The testicles/testes, may be limited to suppressing the influence of the treatment on the results of the study activity of Sertoli cells (Roser, 2008). This stands was not explained by the authors. Therefore, it seems in partial contrast to the findings of other authors, sound to examine only the horses which did not un- who state that although POMC gene expression in dergo any pain alleviation treatment. The concentra- epididymides and testes was not observed in stal- tions of beta-endorphin in cured animals were lower lions, the presence of beta-endorphin was found in than in the deceased ones as well as animals which these organs using immunocytochemical staining had to be euthanized due to the lack of effect of the (Soverchia et al., 2006). These results may suggest treatment (12.29 and 34.57 pmol/l, respectively). The plasma as the source of the peptide rather than assessment of the peptide concentration may have testes or epididymides, and are not sufficient, in a vast prognostic significance. In healthy horses the the light of the current state of knowledge, to fully value was 5.71 pmol/l, while in the diseased animals explain the role of beta-endorphin in the function- with mild, moderate and acute clinical symptoms ing of the reproductive system in stallions. the values were 11.43, 14.0 and 32.29 pmol/l, respec- The role of endogenous opioids in females ap- tively. The results of the examination conducted af- pears to be complex. Reliable research, employing ter the animals were brought to hospital, with the naloxone – an opioid receptor blocker, was con- abovementioned influence of transportation on the ducted in mares (Behrens et al., 1993).
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